Metabolism of alcohol involves a two step enzymatic reaction. First, alcohol is oxidized to acetaldehyde by alcohol dehydrogenase. Second, the acetaldehyde is oxidized to acetic acid by acetaldehyde dehydrogenase and glutathione. Acetic acid is then transported to the muscles and adipose tissue where it is further broken down into carbon dioxide and water. Thus, the rate at which alcohol is metabolized to acetic acid depends in part upon the balance of both alcohol dehydrogenase and acetaldehyde dehydrogenase. This balance is important because although alcohol is toxic to the body, acetaldehyde is actually more toxic than alcohol.
Polymorphisms in the acetaldehyde dehydrogenase gene correlate significantly to particular populations, such as those having Asian ancestry and even more significantly to those having Japanese ancestry. These polymorphisms frequently result in slowed conversion of acetaldehyde to acetic acid. Accordingly, without significant slowing of alcohol dehydrogenase activity, acetaldehyde begins to build up in the body. Rapid accumulation of acetaldehyde causes redness in the skin, primarily along the face and limbs. This condition is referred to as alcohol-induced flush reaction, also known as Asian flush.
A combination treatment for controlling alcohol-induced flush reaction is proposed in published U.S. patent application Ser. No. 11/009,559. Specifically, the authors propose a combined treatment prior to imbibing in alcohol, the treatment including administering both an H1 receptor histamine antagonist and a H2 receptor histamine antagonist. The proposed H1 receptor antagonists include terfenadine, astemisole and fenoxifene. The proposed H2 receptor antagonists included cimetidine, famotidine, nizatidine and ranitidine. Such treatments do not address the conversion of alcohol to acetic acid but instead propose to competitively antagonize H1 and H2 histidine receptors while in circulation, which temporarily reduces the appearance of symptoms. However, the proposed treatments suffer from two drawbacks. First, many that suffer from alcohol-induced flush reaction do not respond to many of the proposed antagonists, which indicates the antagonists are not interchangeable. Second, in some instances temporarily masking symptoms may lead to increased alcohol consumption, which may intensify deleterious effects once temporary relief ends.
Although alcohol-induced flush reaction is typically associated with redness that occurs relatively shortly after consumption of alcohol, the build up of acetaldehyde also contributes to hangover, which is often felt by many the morning after alcohol consumption. Common hangover effects include headache, nausea, dizziness, fatigue, thirst, tension, anxiety, paleness, tremor and perspiration. It is commonly believed that black coffee or further consumption of alcohol in the morning reduces the symptoms; however, the effectiveness varies across individuals.
Accordingly, there remains a need to develop new methods and compositions for the treatment and prevention of deleterious effects associated with alcohol consumption.